P185Expression of osmosensing water channel aquaporin-1 and cytoskeleton remodeling associated with endotoxin-induced myocardial dysfunction in aging mice

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Sepsis is characterized by impairment in cardiac function, which further declines with aging. We analyzed the impact of aging on expression of key regulatory genes of cardiac cytoskeleton and vascular permeability, such as gelsolin and aquaporin-1 (AQP1) respectively, along with key regulatory genes of inflammation such as inducible nictric oxide synthase (iNOS) during endotoxic stress, and how they correlates with endotoxic-stress induced cardiac dysfunction.

Methods and Results

Senescent (24 months) and young (3 months) male mice were treated i.p. with saline or lipopolysaccharide (LPS, 30 mg/Kg). Cardiac function and cardiac morphometry were analyzed by echocardiography at baseline and 2 and 24 hours after injections. Mice were sacrified and cardiac proteins collected for the analysis of expression of total and cardiac-specific actin, gelsolin, AQP1, iNOS, nitric oxide production, and signal transducers and activators of transcription-3 (STAT3). LPS administration decreased contractility and increased cardiac dimensions, which were greater in senescent animals compared with young mice. These changes were paralleled by decreased expression of actins in the heart tissue, along with up-regulation of gelsolin and AQP1, and by a concomitant increase of iNOS and phosphorylated STAT3, with a maximum effect at 24 hours after LPS injection.


Endotoxic stress decreased cardiac actin expression and induced gelsolin, AQP1 and pro-inflammatory genes, such as iNOS. Modulation of the expression of these genes may be causally associated with the elevated susceptibility to cardiac dysfunction in aged patients during inflammatory stress.

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